{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:35:12Z","timestamp":1793144112857,"version":"4.5.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100015720","name":"Universidad de Extremadura","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015720","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Biometeorol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Balneotherapy using peloids (mud-bath therapy) is one of the most effective non-pharmacological approaches for managing osteoarticular and musculoskeletal disorders, such as osteoarthritis (OA). Recent studies have shown that peloids enriched with rosmarinic acid (RosA) enhance the therapeutic effects of mud therapy in elderly OA patients. The objective of this study was to evaluate whether the normalization of the interaction between the hormetic stress response, mediated by cortisol, and the inflammatory response, mediated by IL-8 (measured in blood by ELISA), underlies the clinical benefits of a hyperthermic mud-bath intervention using a RosA-enriched peloid, a polyphenolic acid with anti-inflammatory and immunomodulatory properties. Additionally, we aimed to investigate whether this neuroimmune regulation contributes to enhancing the innate immune response, specifically the phagocytic and microbicidal activity of neutrophils (assessed by flow cytometry). Twenty-three elderly OA patients participated in the mud-bath intervention, a 10-day cycle of hyperthermic balneotherapy using a RosA-fortified peloid and mineral medicinal water at 40\u00a0\u00b0C. Significant increases in systemic cortisol levels, along with a notable decrease in IL-8 and enhanced phagocytic and microbicidal activity of neutrophils, were observed following the intervention. These effects were accompanied by improved knee mobility and reduced pain. In conclusion, hyperthermic mud-bath therapy with a RosA-enriched peloid induces immunoneuroendocrine stabilization, which underlies the clinical benefits of the balneological intervention. Finally, concepts such as neuroimmunomodulation, hormesis, and the bioregulation of the innate and inflammatory immune responses in the context of balneotherapy are also discussed.<\/jats:p>","DOI":"10.1007\/s00484-025-02984-7","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T08:51:57Z","timestamp":1752655917000},"page":"2115-2124","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neuroimmunomodulation induced by mud-bath therapy: clinical benefits and bioregulation of the innate\/inflammatory responses induced by a peloid enriched with rosmarinic acid in elderly patients with osteoarthritis"],"prefix":"10.1007","volume":"69","author":[{"given":"Eduardo","family":"Ortega-Collazos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Otero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casimiro","family":"L\u00f3pez-Jurado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Mart\u00edn-Cordero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"G\u00e1lvez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Torres-Piles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7007-7615","authenticated-orcid":false,"given":"Eduardo","family":"Ortega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Hinchado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"2984_CR1","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1002\/art.1780290816","volume":"29","author":"R Altman","year":"1986","unstructured":"Altman R, Asch E, Bloch D et al (1986) Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and therapeutic criteria committee of the American rheumatism association. Arthritis Rheum 29:1039\u20131049. https:\/\/doi.org\/10.1002\/art.1780290816","journal-title":"Arthritis Rheum"},{"key":"2984_CR2","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1007\/s00484-018-1504-8","volume":"62","author":"M Antonelli","year":"2018","unstructured":"Antonelli M, Donelli D (2018) Effects of balneotherapy and spa therapy on levels of cortisol as a stress biomarker: a systematic review. Int J Biometeorol 62:913\u2013924. https:\/\/doi.org\/10.1007\/s00484-018-1504-8","journal-title":"Int J Biometeorol"},{"issue":"10","key":"2984_CR3","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1007\/s00484-024-02721-6","volume":"68","author":"M Antonelli","year":"2024","unstructured":"Antonelli M, Fasano F, Veronesi L, Donelli D, Vitale M, Pasquarella C (2024) Balneotherapy and cortisol levels: an updated systematic review and meta-analysis. Int J Biometeorol 68(10):1909\u20131922. https:\/\/doi.org\/10.1007\/s00484-024-02721-6","journal-title":"Int J Biometeorol"},{"key":"2984_CR4","first-page":"840","volume":"12","author":"M Aydin","year":"2024","unstructured":"Aydin M, Avci GA, Yilmaz UI et al (2024) Evaluation of oxidative stress and cellular immunity in grades III-IV knee osteoarthritis. Arch Bone Jt Surg 12:840","journal-title":"Arch Bone Jt Surg"},{"key":"2984_CR5","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1046\/j.1365-2826.2002.00823.x","volume":"14","author":"C Barriga","year":"2002","unstructured":"Barriga C, Mart\u00edn MI, Ortega E, Rodriguez AB (2002) Physiological concentrations of melatonin and corticosterone in stress and their relationship with phagocytic activity. J Neuroendocrinol 14:691\u2013695. https:\/\/doi.org\/10.1046\/j.1365-2826.2002.00823.x","journal-title":"J Neuroendocrinol"},{"key":"2984_CR6","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.joca.2012.11.012","volume":"21","author":"F Berenbaum","year":"2013","unstructured":"Berenbaum F (2013) Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil 21:16\u201321. https:\/\/doi.org\/10.1016\/j.joca.2012.11.012","journal-title":"Osteoarthr Cartil"},{"key":"2984_CR7","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.taap.2007.02.015","volume":"222","author":"EJ Calabrese","year":"2007","unstructured":"Calabrese EJ, Bachmann KA, Bailer AJ et al (2007) Biological stress response terminology: integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol Appl Pharmacol 222:122\u2013128. https:\/\/doi.org\/10.1016\/j.taap.2007.02.015","journal-title":"Toxicol Appl Pharmacol"},{"key":"2984_CR8","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/j.clay.2010.02.016","volume":"48","author":"MI Carretero","year":"2010","unstructured":"Carretero MI, Pozo M, Mart\u00edn-Rub\u00ed JA et al (2010) Mobility of elements in interaction between artificial sweat and peloids used in Spanish spas. Appl Clay Sci 48:506\u2013515","journal-title":"Appl Clay Sci"},{"key":"2984_CR9","doi-asserted-by":"publisher","first-page":"8054","DOI":"10.1007\/s11356-021-17780-0","volume":"29","author":"S Cheleschi","year":"2022","unstructured":"Cheleschi S, Tenti S, Seccafico I et al (2022) Balneotherapy year in review 2021: focus on the mechanisms of action of balneotherapy in rheumatic diseases. Environ Sci Pollut Res Int 29:8054\u20138073. https:\/\/doi.org\/10.1007\/s11356-021-17780-0","journal-title":"Environ Sci Pollut Res Int"},{"issue":"12","key":"2984_CR10","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1089\/jmf.2013.0189z","volume":"17","author":"AE Connelly","year":"2014","unstructured":"Connelly AE, Tucker AJ, Tulk H et al (2014) High-rosmarinic acid spearmint tea in the management of knee osteoarthritis symptoms. J Med Food 17(12):1361\u20131367. https:\/\/doi.org\/10.1089\/jmf.2013.0189z","journal-title":"J Med Food"},{"key":"2984_CR11","doi-asserted-by":"publisher","first-page":"3966","DOI":"10.2174\/138161211798764861","volume":"17","author":"M De la Fuente","year":"2011","unstructured":"De la Fuente M, Cruces J, Hernandez O, Ortega E (2011) Strategies to improve the functions and redox state of the immune system in aged subjects. Curr Pharm Des 17:3966\u20133993. https:\/\/doi.org\/10.2174\/138161211798764861","journal-title":"Curr Pharm Des"},{"key":"2984_CR12","doi-asserted-by":"publisher","DOI":"10.1007\/s003930070015","author":"A del Rey","year":"2000","unstructured":"del Rey A, Besedovsky HO (2000) The cytokine-HPA axis circuit contributes to prevent or moderate autoimmune processes. Z Rheumatol. https:\/\/doi.org\/10.1007\/s003930070015. 59 Suppl 2:II\/31\u2013\u20095","journal-title":"Z Rheumatol"},{"key":"2984_CR13","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.reuma.2012.09.005","volume":"9","author":"L Espejo Ant\u00fanez","year":"2013","unstructured":"Espejo Ant\u00fanez L, Caro Pu\u00e9rtolas B, Ib\u00e1\u00f1ez Burgos B et al (2013) Effects of mud therapy on perceived pain and quality of life related to health in patients with knee osteoarthritis. Reumatol Clin 9:156\u2013160. https:\/\/doi.org\/10.1016\/j.reuma.2012.09.005","journal-title":"Reumatol Clin"},{"key":"2984_CR14","doi-asserted-by":"publisher","first-page":"101291","DOI":"10.1016\/j.mam.2024.101291","volume":"98","author":"J F\u00e9lix","year":"2024","unstructured":"F\u00e9lix J, Mart\u00ednez de Toda I, D\u00edaz-Del Cerro E et al (2024) Frailty and biological age. Which best describes our aging and longevity? Mol Aspects Med 98:101291. https:\/\/doi.org\/10.1016\/j.mam.2024.101291","journal-title":"Mol Aspects Med"},{"key":"2984_CR15","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1007\/s00484-014-0943-0","volume":"59","author":"A Fioravanti","year":"2015","unstructured":"Fioravanti A, Bacaro G, Giannitti C et al (2015) One-year follow-up of mud-bath therapy in patients with bilateral knee osteoarthritis: a randomized, single-blind controlled trial. Int J Biometeorol 59:1333\u20131343. https:\/\/doi.org\/10.1007\/s00484-014-0943-0","journal-title":"Int J Biometeorol"},{"key":"2984_CR16","first-page":"78","volume":"17","author":"I Galvez","year":"2017","unstructured":"Galvez I, Torres-Piles S, D. Hinchado M et al (2017) Immune-neuroendocrine dysregulation in patients with osteoarthritis: a revision and a pilot study. Endocrine, metab immune Disord targets (Formerly curr drug targets-Immune. Endocr Metab Disord 17:78\u201385","journal-title":"Endocr Metab Disord"},{"key":"2984_CR17","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.3390\/ijms19061687","volume":"19","author":"I G\u00e1lvez","year":"2018","unstructured":"G\u00e1lvez I, Torres-Piles S, Ortega-Rinc\u00f3n E (2018a) Balneotherapy, immune system, and stress response: a hormetic strategy?. Int J Mol Sci 19:1687","journal-title":"Int J Mol Sci"},{"key":"2984_CR18","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1080\/02656736.2018.1502896","volume":"35","author":"I G\u00e1lvez","year":"2018","unstructured":"G\u00e1lvez I, Torres-Piles S, Ortega E (2018b) Innate\/inflammatory bioregulation and clinical effectiveness of whole-body hyperthermia (balneotherapy) in elderly patients with osteoarthritis. Int J Hyperth 35:340\u2013347","journal-title":"Int J Hyperth"},{"key":"2984_CR19","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1007\/s00484-019-01748-4","volume":"64","author":"I G\u00e1lvez","year":"2020","unstructured":"G\u00e1lvez I, Torres-Piles S, Ortega E (2020) Effect of mud-bath therapy on the innate\/inflammatory responses in elderly patients with osteoarthritis: a discussion of recent results and a pilot study on the role of the innate function of monocytes. Int J Biometeorol 64:927\u2013935. https:\/\/doi.org\/10.1007\/s00484-019-01748-4","journal-title":"Int J Biometeorol"},{"key":"2984_CR20","doi-asserted-by":"publisher","first-page":"3292","DOI":"10.3390\/molecules27103292","volume":"27","author":"H Guan","year":"2022","unstructured":"Guan H, Luo W, Bao B et al (2022) A comprehensive review of Rosmarinic acid: from phytochemistry to Pharmacology and its new insight. Molecules 27:3292","journal-title":"Molecules"},{"key":"2984_CR21","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1007\/s10067-009-1114-2","volume":"28","author":"T Harzy","year":"2009","unstructured":"Harzy T, Ghani N, Akasbi N et al (2009) Short-and long-term therapeutic effects of thermal mineral waters in knee osteoarthritis: a systematic review of randomized controlled trials. Clin Rheumatol 28:501\u2013507","journal-title":"Clin Rheumatol"},{"key":"2984_CR22","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/j.1748-1716.1994.tb09689.x","volume":"150","author":"D Je\u017eova","year":"1994","unstructured":"Je\u017eova D, Kvet\u0148ansk\u00fd R, Viga\u0161 M (1994) Sex differences in endocrine response to hyperthermia in sauna. Acta Physiol Scand 150:293\u2013298","journal-title":"Acta Physiol Scand"},{"key":"2984_CR23","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nrrheum.2010.196","volume":"7","author":"M Kapoor","year":"2011","unstructured":"Kapoor M, Martel-Pelletier J, Lajeunesse D et al (2011) Role of Proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 7:33\u201342","journal-title":"Nat Rev Rheumatol"},{"key":"2984_CR24","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1001\/jama.2020.22171","volume":"325","author":"JN Katz","year":"2021","unstructured":"Katz JN, Arant KR, Loeser RF (2021) Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA 325:568\u2013578","journal-title":"JAMA"},{"issue":"7","key":"2984_CR25","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1002\/art.24598","volume":"60","author":"G Livshits","year":"2009","unstructured":"Livshits G, Zhai G, Hart DJ et al (2009) Interleukin-6 is a significant predictor of ratdiographic knee osteoarthritis: the Chingford study. Arthritis Rheum 60(7):2037\u20132045. https:\/\/doi.org\/10.1002\/art.24598","journal-title":"Arthritis Rheum"},{"key":"2984_CR26","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3389\/fphar.2020.00153","volume":"11","author":"C Luo","year":"2020","unstructured":"Luo C, Zou L, Sun H, Peng J et al (2020) A review of the Anti-Inflammatory effects of Rosmarinic acid on inflammatory diseases. Front Pharmacol 11:153. https:\/\/doi.org\/10.3389\/fphar.2020.00153","journal-title":"Front Pharmacol"},{"key":"2984_CR27","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1007\/s11332-021-00778-z","volume":"17","author":"MC Maccarone","year":"2021","unstructured":"Maccarone MC, Magro G, Solimene U et al (2021) From in vitro research to real life studies: an extensive narrative review of the effects of balneotherapy on human immune response. Sport Sci Health 17:817\u2013835. https:\/\/doi.org\/10.1007\/s11332-021-00778-z","journal-title":"Sport Sci Health"},{"key":"2984_CR28","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.bbr.2018.07.010","volume":"353","author":"KB Makhathini","year":"2018","unstructured":"Makhathini KB, Mabandla MV, Daniels WMU (2018) Rosmarinic acid reverses the deleterious effects of repetitive stress and Tat protein. Behav Brain Res 353:203\u2013209. https:\/\/doi.org\/10.1016\/j.bbr.2018.07.010","journal-title":"Behav Brain Res"},{"key":"2984_CR29","doi-asserted-by":"crossref","unstructured":"Matsumoto T, Nishiyama T, Nishimura N et al (2001) Endocrine responses to heat and cold stress. Thermother neoplasia, inflammation, pain 228\u2013241","DOI":"10.1007\/978-4-431-67035-3_26"},{"key":"2984_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.arr.2007.08.007","volume":"7","author":"MP Mattson","year":"2008","unstructured":"Mattson MP (2008) Hormesis defined. Ageing Res Rev 7:1\u20137. https:\/\/doi.org\/10.1016\/j.arr.2007.08.007","journal-title":"Ageing Res Rev"},{"key":"2984_CR31","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1111\/j.1365-2265.1989.tb00271.x","volume":"30","author":"N M\u00f8ller","year":"1989","unstructured":"M\u00f8ller N, Beckwith R, Butler PC et al (1989) Metabolic and hormonal responses to exogenous hyperthermia in man. Clin Endocrinol (Oxf) 30:651\u2013660","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2984_CR32","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s13105-016-0478-4","volume":"72","author":"E Ortega","year":"2016","unstructured":"Ortega E (2016) The bioregulatory effect of exercise on the innate\/inflammatory responses. J Physiol Biochem 72:361\u2013369. https:\/\/doi.org\/10.1007\/s13105-016-0478-4","journal-title":"J Physiol Biochem"},{"key":"2984_CR33","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/BF00863397","volume":"66","author":"E Ortega","year":"1993","unstructured":"Ortega E, Barriga C, De la Fuente M (1993) Study of the phagocytic process in neutrophils from elite sportswomen. Eur J Appl Physiol Occup Physiol 66:37\u201342","journal-title":"Eur J Appl Physiol Occup Physiol"},{"key":"2984_CR34","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1007\/s00484-017-1361-x","volume":"61","author":"E Ortega","year":"2017","unstructured":"Ortega E, G\u00e1lvez I, Hinchado MD et al (2017) Anti-inflammatory effect as a mechanism of effectiveness underlying the clinical benefits of pelotherapy in osteoarthritis patients: regulation of the altered inflammatory and stress feedback response. Int J Biometeorol 61:1777\u20131785","journal-title":"Int J Biometeorol"},{"key":"2984_CR35","doi-asserted-by":"crossref","unstructured":"Ortega E, G\u00e1lvez I, Mart\u00edn-Cordero L (2018) Extracellular Hsp70 and low-grade inflammation-and stress-related pathologies. Heat Shock Proteins Stress 13\u201338","DOI":"10.1007\/978-3-319-90725-3_2"},{"key":"2984_CR36","doi-asserted-by":"publisher","first-page":"12017","DOI":"10.3390\/app142412017","volume":"14","author":"E Ortega-Collazos","year":"2024","unstructured":"Ortega-Collazos E, Hinchado MD, Otero E et al (2024) Balneotherapy (Mud-Bath Therapy) with a peloid enriched with Rosmarinic acid enhances clinical outcomes and innate immune benefits in elderly patients with osteoarthritis: A pilot study. Appl Sci 14:12017","journal-title":"Appl Sci"},{"key":"2984_CR37","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.clay.2013.08.034","volume":"83","author":"M Pozo","year":"2013","unstructured":"Pozo M, Carretero MI, Maraver F et al (2013) Composition and physico-chemical properties of peloids used in Spanish spas: a comparative study. Appl Clay Sci 83:270\u2013279","journal-title":"Appl Clay Sci"},{"key":"2984_CR38","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.bone.2016.01.019","volume":"85","author":"M Rahmati","year":"2016","unstructured":"Rahmati M, Mobasheri A, Mozafari M (2016) Inflammatory mediators in osteoarthritis: A critical review of the state-of-the-art, current prospects, and future challenges. Bone 85:81\u201390","journal-title":"Bone"},{"key":"2984_CR39","doi-asserted-by":"publisher","first-page":"dose","DOI":"10.2203\/dose-response.09-041.Rattan","volume":"8","author":"SIS Rattan","year":"2010","unstructured":"Rattan SIS, Demirovic D (2010) Hormesis can and does work in humans. Dose-Response 8:dose\u2013response","journal-title":"Dose-Response"},{"key":"2984_CR40","first-page":"728","volume":"18","author":"L-E Stanciu","year":"2017","unstructured":"Stanciu L-E, Pascu EI, Ionescu E-V et al (2017) Anti-ageing potential of Techirghiol mud therapy through the modulation of pituitary-adrenal axis activity. J Env Prot Ecol 18:728\u2013736","journal-title":"J Env Prot Ecol"},{"issue":"11","key":"2984_CR41","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1016\/j.joca.2010.08.016","volume":"18","author":"O Stannus","year":"2010","unstructured":"Stannus O, Jones G, Cicuttini F et al (2010) Circulating levels of IL-6 and TNF-\u03b1 are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthritis Cartilage 18(11):1441\u20131447. https:\/\/doi.org\/10.1016\/j.joca.2010.08.016","journal-title":"Osteoarthritis Cartilage"},{"key":"2984_CR42","doi-asserted-by":"publisher","first-page":"11","DOI":"10.2220\/biomedres.27.11","volume":"27","author":"M Toda","year":"2006","unstructured":"Toda M, Morimoto K, Nagasawa S, Kitamura K (2006) Change in salivary physiological stress markers by spa bathing. Biomed Res 27:11\u201314","journal-title":"Biomed Res"},{"key":"2984_CR43","doi-asserted-by":"publisher","first-page":"7379","DOI":"10.3390\/app12157379","volume":"12","author":"L Tognolo","year":"2022","unstructured":"Tognolo L, Coraci D, Fioravanti A et al (2022) Clinical impact of balneotherapy and therapeutic exercise in rheumatic diseases: a lexical analysis and scoping review. Appl Sci 12:7379","journal-title":"Appl Sci"},{"key":"2984_CR44","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.joca.2020.01.016","volume":"28","author":"MHJ Van den Bosch","year":"2020","unstructured":"Van den Bosch MHJ, Van Lent P, Van Der Kraan PM (2020) Identifying effector molecules, cells, and cytokines of innate immunity in OA. Osteoarthr Cartil 28:532\u2013543","journal-title":"Osteoarthr Cartil"}],"container-title":["International Journal of Biometeorology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00484-025-02984-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00484-025-02984-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00484-025-02984-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T20:05:07Z","timestamp":1759176307000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00484-025-02984-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,16]]},"references-count":44,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["2984"],"URL":"https:\/\/doi.org\/10.1007\/s00484-025-02984-7","relation":{},"ISSN":["0020-7128","1432-1254"],"issn-type":[{"value":"0020-7128","type":"print"},{"value":"1432-1254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,16]]},"assertion":[{"value":"25 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Ethical Committee of the University of Extremadura, Spain, under the guidelines of the European Community Council Directives and the Helsinki Declaration (N\u00ba Reg. 96\/2022 and N\u00ba Reg 146\/2024).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all subjects involved in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Consent to publication"}},{"value":"The authors declare that they have no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}